The prostaglandins are currently of great interest because of the broad physiological responses which they elicit in animals, including man.
Development of the potential application of both natural and synthetic prostaglandins relies upon efficient chemical synthetic methods being available. See, Mitra, "The Synthesis of Prostaglandins", Wiley, N.Y. 1977.
Processes for preparing prostaglandins and their analogs via conjugate addition of an alkenyl moiety to the unsaturated ketone functionality of a substituted cyclopentenone have been described in U.S. Pat. Nos. 3,965,143, 3,950,406 and 4,233,231, and Tet. Letters, 2063 (1977); Prostaglandins, 10,733 (1975) and J. Amer. Chem. Soc., 97, 857 (1975). Such reactions usually involve the use of alkenyl lithium compounds as intermediates in the formation of alkenylcuprates, the latter being capable of the desired conjugate addition reaction. Extensive research has been done aimed at developing species which could duplicate beneficial aspects of cuprate chemistry while not relying on lithium reagent precursors. Implementation of lithium-based cuprate processes is often hampered by the tedious preparation of these organolithium precursors. In the special case of alkenylcuprates, important to the synthesis of various natural products, it is necessary to generate and maintain stereochemically pure alkenyl species. Alkenyllithium reagents used to prepare the corresponding cuprates are obtained by metal-halogen exchange with the corresponding alkenylhalide or by reaction of these organic halides with lithium metal. Although the conversion of alkenylhalides to alkenyllithium reagents occurs predominantly with retention of configuration, some loss of double-bond stereochemistry can occur. Lastly, alkenylcuprate species are generally utilized at low temperatures since they are thermally unstable.
The possibility of activating organozirconium species toward conjugate addition using a second metallic species catalytically, and the use of the activated species for the synthesis of 15-hydroxy prostaglandin analogs were realized by J. Schwartz, et al., J. Amer. Chem. Soc. 102 1333 (1980). However, the prior art does not disclose an organozirconium species useful in a conjugate addition reaction directed to the preparation of 15-deoxy-16-hydroxy-16-substituted prostaglandins.